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Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy
Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype–phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To dete...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616419/ https://www.ncbi.nlm.nih.gov/pubmed/34831173 http://dx.doi.org/10.3390/cells10112950 |
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author | Schuldt, Maike van Driel, Beau Algül, Sila Parbhudayal, Rahana Y. Barge-Schaapveld, Daniela Q. C. M. Güçlü, Ahmet Jansen, Mark Michels, Michelle Baas, Annette F. van de Wiel, Mark A. Nieuwdorp, Max Levin, Evgeni Germans, Tjeerd Jans, Judith J. M. van der Velden, Jolanda |
author_facet | Schuldt, Maike van Driel, Beau Algül, Sila Parbhudayal, Rahana Y. Barge-Schaapveld, Daniela Q. C. M. Güçlü, Ahmet Jansen, Mark Michels, Michelle Baas, Annette F. van de Wiel, Mark A. Nieuwdorp, Max Levin, Evgeni Germans, Tjeerd Jans, Judith J. M. van der Velden, Jolanda |
author_sort | Schuldt, Maike |
collection | PubMed |
description | Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype–phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics. |
format | Online Article Text |
id | pubmed-8616419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86164192021-11-26 Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy Schuldt, Maike van Driel, Beau Algül, Sila Parbhudayal, Rahana Y. Barge-Schaapveld, Daniela Q. C. M. Güçlü, Ahmet Jansen, Mark Michels, Michelle Baas, Annette F. van de Wiel, Mark A. Nieuwdorp, Max Levin, Evgeni Germans, Tjeerd Jans, Judith J. M. van der Velden, Jolanda Cells Article Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype–phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics. MDPI 2021-10-29 /pmc/articles/PMC8616419/ /pubmed/34831173 http://dx.doi.org/10.3390/cells10112950 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Schuldt, Maike van Driel, Beau Algül, Sila Parbhudayal, Rahana Y. Barge-Schaapveld, Daniela Q. C. M. Güçlü, Ahmet Jansen, Mark Michels, Michelle Baas, Annette F. van de Wiel, Mark A. Nieuwdorp, Max Levin, Evgeni Germans, Tjeerd Jans, Judith J. M. van der Velden, Jolanda Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
title | Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
title_full | Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
title_fullStr | Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
title_full_unstemmed | Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
title_short | Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy |
title_sort | distinct metabolomic signatures in preclinical and obstructive hypertrophic cardiomyopathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616419/ https://www.ncbi.nlm.nih.gov/pubmed/34831173 http://dx.doi.org/10.3390/cells10112950 |
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